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Predictive Value of the Neutrophil-to-Lymphocyte Ratio(NLR) for Diagnosis and Worse Clinical Course of the COVID-19: Findings from Ten Provinces in China

43 Pages Posted: 14 Apr 2020

See all articles by Yan Ma

Yan Ma

China Academy of Chinese Medical Sciences

Nannan Shi

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Yipin Fan

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Jingya Wang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Chen Zhao

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Guangxi Li

China Academy of Chinese Medical Sciences - Guang'anmen Hospital

Xiaofeng Zhang

Heilongjiang Administration Bureau of Traditional Chinese Medicine

Weiguo Bai

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Furong Xiao

Harbin Infectious Disease Hospital

Jingwei Wang

Harbin Infectious Disease Hospital

Hui Na

Harbin Infectious Disease Hospital

Quntang Li

Chongqing Traditional Chinese Medicine Hospital

Mei Shi

Anhui University of Chinese Medicine - Department of Infection

Nong Tang

Guangxi University of Chinese Medicine (GXTCM) - Department of Traditional Chinese Medicine

Jin Huang

Guangxi University of Chinese Medicine (GXTCM) - Department of Traditional Chinese Medicine

Shaozhen Huang

Fangchenggang First People's Hospital - Department of Traditional Chinese Medicine

Haihao Jin

Liuzhou People's Hospital

Baihua Jiang

Heilongjiang Academy of Medical Sciences

Hongming Xu

Daqing Second Hospital

Tianqing Zhu

The Greater Khingan Range People’s Hospital

Shoufang Xu

Jiamusi Infectious Disease Hospital

Yanhua Xiao

Mudanjiang Kangan Hospital

Qiao Feng

The People's Hospital of QiTaiHe

Shusen Zhao

Qiqihar Institute for the Prevention and Treatment of Infectious Disease

Hong Chen

First Hospital of Qiqihar

Yingchun Zhou

Shuangyashan People's Hospital

Zhang Liu

First Hospital of Suihua City

Huaben Zhang

The Third People's Hospital of Xining

Dongting Wang

Datong Fourth Hospital

Yinzhen Wang

Jincheng People's Hospital

Xiaoyan Wang

Jinzhong Infectious Disease Hospital

Fangli Song

The Third People's Hospital of Linfen

Kai Zheng

Fenyang Hospital of Shanxi Province

Lanping Wu

Shuozhou People's Hospital

Jinping Liu

Government of the People's Republic of China - Taiyuan Fourth People's Hospital

Haijun Xie

Xinzhou People's Hospital

Ruixia Xue

Yuncheng Second Hospital

Guifen Hu

Changzhi Medical College - Heping Hospital

Ya Mao

Ankang Hospital of Traditional Chinese Medicine

Gongqi Zhang

Baoji Central Hospital

Wei Wu

Hanzhong Central Hospital

Puye Yang

Shaanxi Infectious Disease Hospital

Mingbo Yang

Shaanxi Infectious Disease Hospital

Liying Chen

Shangluo Central Hospital

Jinbo Zhang

Xian Chest Hospital

Tuanmao Guo

Xianyang Central Hospital

Yuanjun Li

Yan'an Second People's Hospital

Jiangfeng Bai

Yulin Chinese Medicine Hospital

Xiao Lei

North Sichuan Medical College - First Affiliated Hospital

Minqing Li

Dazhou Central Hospital

Linsong Zhang

Southwest Medical University - Affiliated Hospital

Junteng Zhu

Putian University - Affiliated Hospital

Sheng Sun

Chengde Hospital of Traditional Chinese Medicine

Xiaomei Hu

Langfang Hospital of Chinese Medicine

Yunhong Hu

Xingtai Hospital of Chinese Medicine

Shengli Yuan

Zhangjiakou Hospital of Traditional Chinese Medicine

Lin Tong

China Academy of Chinese Medical Sciences - Institute of Information on Traditional Chinese Medicine

Sihong Liu

China Academy of Chinese Medical Sciences - Institute of Information on Traditional Chinese Medicine

Renbo Chen

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Zhan Shi

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Li Li

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Jia Liu

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Hao Gu

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Yingjie Zhi

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Zhifei Wang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Yuanyuan Li

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Ning Liang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Huizhen Li

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Liwen Jiao

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Ruili Huo

China Academy of Chinese Medical Sciences - Department of Scientific Research

Yongyan Wang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Yanping Wang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Huamin Zhang

China Academy of Chinese Medical Sciences - Institute of Chinese Materia Medica

Wei Wang

Beijing University of Chinese Medicine

More...

Abstract

Background: Novel coronavirus pneumonia (NCP) is often changing rapidly and fatal. Early detection and early triage of coronavirus disease 2019 (Covid-19) is the key to success management of the disease. An easily obtainable yet accurate variable for both diagnosis and prognosis is urgently needed. We aim to report predictive Value of the Neutrophil-to-Lymphocyte Ratio(NLR) for diagnosis and worse clinical course of the COVID-19, which have not been well demonstrated.

Methods: Our study consisted of two stages, at the first stage, a retrospective, single-center, cohort study including was conducted in Heilongjiang, on admission, demographic, clinical, and laboratory data were collected and compared between patients with COVID-19 and patients with non COVID-19; we used multivariable logistic regression methods to explore the risk factors associated with COVID-19;A receiver operating characteristic(ROC) analysis was conducted to calculate the area under the curve(AUC) to assess predictive value of NLR for diagnosis of COVID 19. At the second stage, we conducted retrospective, multi-center and large sample study in 43 hospitals from ten provinces of China, COVID-19 patients with laboratory-confirmed divided into three groups including mild cases, ordinary cases and severe cases. Multivariate logistic regression methods were used to identify the risk factors for the deterioration of COVID-19, along with, a receiver operating characteristic (ROC) curve was also drawn to assess impact on the clinical course of the COVID-19.

Findings: We recruited a total of 635 patients with COVID-19 and 27 cases with non COVID-19(Viral pneumonia) from 28 January to 25 February. A total of 88 cases were enrolled with a retrospective, single-center, cohort study from Heilongjiang province, of these, COVID-19 cases were 61(69%) and non COVID-19 cases were 27(31%). On admission, fever (69%) was the most common symptoms, cough (56%) and fatigue(53%). An average(SD) of NLR of COVID-19 patients and non- COVID-19 patients were3.48±2.04 and 2.21±1.14, respectively. multivariable regression showed increasing odds of COVID-19 patients associated with NLR(odds ratio 1.752, 95% CI 1.111-2.763, per 1 unit increase; p=0.016). In addition, the area under the curve (AUC) of NLR was 0.707 and cutoff value was 2.22. At the second stage, 635 patients with COVID were enrolled with a retrospective, multi-center, large sample study in the 43 settings from 10 provinces, of these, mild case were 86(14%), ordinary cases [486(76%)],severe cases[63(10%)], common symptoms was at onset of disease were cough[356(56%)], an average of NLR of 635 patients was 4.04±4.68, and elevated NLR with the deterioration of clinical course[mild case(2.73±2.28), ordinary cases(3.58±3.07), severe cases(9.38±10.52), P<0.0001], in multivariable logistic regression model, compared to mild group, fever(OR 5.739, 95% CI 2.849-11.564) and cough(OR 3.265, 95% CI 1.675-6.331) were associated with ordinary cases, increasing odds of NLR was associated with ordinary cases (OR 1.199, 95% CI 1.010-1.422, per 1 unit increase; p=0.038). Fever(OR 7.587, 95% CI 2.601- 22.132),cough(OR 6.493, 95% CI 2.257-18.682) and shortness of breath(OR 4.133, 95% CI 1.125-15.179) were associated with severe cases, increasing odds of NLR (OR 1.342, 95% CI 1.122-1.605, per 1 unit increase; p=0.001), and increasing odds of age (OR 1.036, 95% CI 1.001- 1.073, per 1 unit increase; p=0.041) were associated with severe cases. The area under the curve (AUC) of NLR was 0.727 and cutoff value was 4.06, additionally, AUC of lymphocytes was 0.719 and cutoff value was 0.765.

Interpretation: NLR as inflammatory markers with rapid, convenient characteristics, NLR≥2.22 could be utilized as a predicting indicator for the early recognition COVID-19 and facilitate detection timely; meanwhile, NLR≥4.06 and lymphocytes≤0.765 were as predicting indicator for severe COVID-19 and can facilitate to further prevent worse progress of clinical course. In addition, cough, shortness of breath, abnormal chest radiological findings were also associated with worse outcome.

Funding Statement: The study was supported by“ National Science and Technology Major Project” (2018ZX10101001-005-003, 2018ZX10101001-005-004).

Declaration of Interests: All authors declare that they have no competing interests.

Ethics Approval Statement: The study was approved by National Administration of Traditional Chinese Medicine, Administration of Traditional Chinese Medicine of 10 provinces and the institutional board of 43 participating setting.

Keywords: COVID-19; Neutrophil-to-Lymphocyte Ratio(NLR); predictive Value; diagnosis; clinical course

Suggested Citation

Ma, Yan and Shi, Nannan and Fan, Yipin and Wang, Jingya and Zhao, Chen and Li, Guangxi and Zhang, Xiaofeng and Bai, Weiguo and Xiao, Furong and Wang, Jingwei and Na, Hui and Li, Quntang and Shi, Mei and Tang, Nong and Huang, Jin and Huang, Shaozhen and Jin, Haihao and Jiang, Baihua and Xu, Hongming and Zhu, Tianqing and Xu, Shoufang and Xiao, Yanhua and Feng, Qiao and Zhao, Shusen and Chen, Hong and Zhou, Yingchun and Liu, Zhang and Zhang, Huaben and Wang, Dongting and Wang, Yinzhen and Wang, Xiaoyan and Song, Fangli and Zheng, Kai and Wu, Lanping and Liu, Jinping and Xie, Haijun and Xue, Ruixia and Hu, Guifen and Mao, Ya and Zhang, Gongqi and Wu, Wei and Yang, Puye and Yang, Mingbo and Chen, Liying and Zhang, Jinbo and Guo, Tuanmao and Li, Yuanjun and Bai, Jiangfeng and Lei, Xiao and Li, Minqing and Zhang, Linsong and Zhu, Junteng and Sun, Sheng and Hu, Xiaomei and Hu, Yunhong and Yuan, Shengli and Tong, Lin and Liu, Sihong and Chen, Renbo and Shi, Zhan and Li, Li and Liu, Jia and Gu, Hao and Zhi, Yingjie and Wang, Zhifei and Li, Yuanyuan and Liang, Ning and Li, Huizhen and Jiao, Liwen and Huo, Ruili and Wang, Yongyan and Wang, Yanping and Zhang, Huamin and Wang, Wei, Predictive Value of the Neutrophil-to-Lymphocyte Ratio(NLR) for Diagnosis and Worse Clinical Course of the COVID-19: Findings from Ten Provinces in China (4/1/2020). Available at SSRN: https://ssrn.com/abstract=3569838 or http://dx.doi.org/10.2139/ssrn.3569838

Yan Ma

China Academy of Chinese Medical Sciences

Dongcheng District
Beijing 100700
China

Nannan Shi

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Yipin Fan

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Jingya Wang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Chen Zhao

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Guangxi Li

China Academy of Chinese Medical Sciences - Guang'anmen Hospital

Beijing
China

Xiaofeng Zhang

Heilongjiang Administration Bureau of Traditional Chinese Medicine

Harbin
China

Weiguo Bai

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Furong Xiao

Harbin Infectious Disease Hospital

Harbin
China

Jingwei Wang

Harbin Infectious Disease Hospital

Harbin
China

Hui Na

Harbin Infectious Disease Hospital

Harbin
China

Quntang Li

Chongqing Traditional Chinese Medicine Hospital

Chongqing
China

Mei Shi

Anhui University of Chinese Medicine - Department of Infection

Hefei, Anhui
China

Nong Tang

Guangxi University of Chinese Medicine (GXTCM) - Department of Traditional Chinese Medicine

Nanning, Guangxi
China

Jin Huang

Guangxi University of Chinese Medicine (GXTCM) - Department of Traditional Chinese Medicine

Nanning, Guangxi
China

Shaozhen Huang

Fangchenggang First People's Hospital - Department of Traditional Chinese Medicine

Fangchenggang
Guangxi
China

Haihao Jin

Liuzhou People's Hospital

Liuzhou, Guangxi
China

Baihua Jiang

Heilongjiang Academy of Medical Sciences

Harbin
China

Hongming Xu

Daqing Second Hospital

Daqing, Heilongjiang
China

Tianqing Zhu

The Greater Khingan Range People’s Hospital

Greater Hinggan, Herilongjiang
China

Shoufang Xu

Jiamusi Infectious Disease Hospital

Jiamusi, Herilongjiang
China

Yanhua Xiao

Mudanjiang Kangan Hospital

Mudanjiang, Herilongjiang
China

Qiao Feng

The People's Hospital of QiTaiHe

QiTaiHe, Herilongjiang
China

Shusen Zhao

Qiqihar Institute for the Prevention and Treatment of Infectious Disease

Qiqihar
China

Hong Chen

First Hospital of Qiqihar

Qiqihar, Herilongjiang
China

Yingchun Zhou

Shuangyashan People's Hospital

Shuangyashan, Herilongjiang
China

Zhang Liu

First Hospital of Suihua City

Suihua City, Herilongjiang
China

Huaben Zhang

The Third People's Hospital of Xining

Xining, Qinghai
China

Dongting Wang

Datong Fourth Hospital

Datong
United States

Yinzhen Wang

Jincheng People's Hospital

Jincheng, Shanxi
China

Xiaoyan Wang

Jinzhong Infectious Disease Hospital

Jinzhong, Shanxi
China

Fangli Song

The Third People's Hospital of Linfen

Linfen, Shanxi
China

Kai Zheng

Fenyang Hospital of Shanxi Province

Fenyang, Shanxi
China

Lanping Wu

Shuozhou People's Hospital

Shuozhou, Shanxi
China

Jinping Liu

Government of the People's Republic of China - Taiyuan Fourth People's Hospital

China

Haijun Xie

Xinzhou People's Hospital

Xinzhou, Shanxi
China

Ruixia Xue

Yuncheng Second Hospital

Yuncheng, Shanxi
China

Guifen Hu

Changzhi Medical College - Heping Hospital

Changzhi, Shanxi
China

Ya Mao

Ankang Hospital of Traditional Chinese Medicine

Ankang, Shanxi
China

Gongqi Zhang

Baoji Central Hospital

8 Jiangtan Road
Baoji, 721008
China

Wei Wu

Hanzhong Central Hospital

Hanzhong
China

Puye Yang

Shaanxi Infectious Disease Hospital

Xian, Shanxi
China

Mingbo Yang

Shaanxi Infectious Disease Hospital

Xian, Shanxi
China

Liying Chen

Shangluo Central Hospital

Shangluo
China

Jinbo Zhang

Xian Chest Hospital

Xian, Shanxi
China

Tuanmao Guo

Xianyang Central Hospital

Xianyang
China

Yuanjun Li

Yan'an Second People's Hospital

Yan'an
China

Jiangfeng Bai

Yulin Chinese Medicine Hospital

Yulin
China

Xiao Lei

North Sichuan Medical College - First Affiliated Hospital

Nanchong
China

Minqing Li

Dazhou Central Hospital

Dazhou
China

Linsong Zhang

Southwest Medical University - Affiliated Hospital

China

Junteng Zhu

Putian University - Affiliated Hospital

Putian, 351100
China

Sheng Sun

Chengde Hospital of Traditional Chinese Medicine

Chengde
China

Xiaomei Hu

Langfang Hospital of Chinese Medicine

Langfang
China

Yunhong Hu

Xingtai Hospital of Chinese Medicine

Xingtai
China

Shengli Yuan

Zhangjiakou Hospital of Traditional Chinese Medicine

Zhangjiakou
China

Lin Tong

China Academy of Chinese Medical Sciences - Institute of Information on Traditional Chinese Medicine

Beijing
China

Sihong Liu

China Academy of Chinese Medical Sciences - Institute of Information on Traditional Chinese Medicine

Beijing
China

Renbo Chen

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Zhan Shi

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Li Li

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Jia Liu

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Hao Gu

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Yingjie Zhi

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Zhifei Wang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Yuanyuan Li

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Ning Liang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Huizhen Li

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Liwen Jiao

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine

Beijing 100700
China

Ruili Huo

China Academy of Chinese Medical Sciences - Department of Scientific Research

Beijing
China

Yongyan Wang (Contact Author)

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine ( email )

Beijing 100700
China

Yanping Wang

China Academy of Chinese Medical Sciences - Institute of Basic Research in Clinical Medicine ( email )

Beijing 100700
China

Huamin Zhang

China Academy of Chinese Medical Sciences - Institute of Chinese Materia Medica ( email )

No. 16, Nanxiaojie
Beijing, 100700
China

Wei Wang

Beijing University of Chinese Medicine ( email )

Beijing, 100029
China

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